EXPLORING THE MECHANISM BEHIND METABOLIC RISK FACTORS FOR ALZHEIMER DISEASE. AN INTEGRATIVE APPROACH TO TYPIFY DISEASE PATHWAYS, OPTMISE DIAGNOSIS AND TREATMENT.
The Swedish Brain Foundation
Alzheimer disease (AD) is the major cause of dementia. Because of the worldwide aging phenomenon of the population, AD has increasing public health relevance. AD is characterised for the accumulation in brain of extracellular amyloid ?-peptide (A?) and intracellular neurofibrillary tangles formed by abnormally hyper-phosphorylated tau (p-tau). Familial AD represents only about 1% of all AD cases. An increasing consensus points AD as multifactorial and heterogenous. The hypothesis that AD is caused by a metabolic imbalance of brain cells has gained increasing experimental support. Type 2 diabetes (T2D), hypertension and high serum cholesterol at midlife increase the risk for AD. Our project aims to explore the molecular links between AD and metabolic impairments, with focus on cholesterol and glucose metabolisms as well as insulin resistance. Our main objectives are: 1) To explore the contribution of metabolic alterations to AD development/progression; 2) To find new biomarkers for AD variant etiologies or subtypes; and 3) To provide information for helping in the design of AD clinical trials, giving emphasis in the selection of the targeted patient population.